Abstract
Euryops pectinatus is a South African ornamental plant belonging to family Asteraceae. The present work evaluates the cytotoxic activity and phytochemical profile of the flower extract. Metabolite profiling was performed using HPLC-PDA-ESI-MS/MS. Total phenolics and flavonoids content were assessed. Cytotoxicity was evaluated against 6 different cancer cell lines using MTT assay. The possible underlying mechanism was proposed. We analyzed whether the extract could overcome the resistance of multidrug-resistant cancer cells for doxorubicin. The effect of combination of E. pectinatus with doxorubicin was also studied. Additionally, the potential inhibitory activity of the identified phytochemicals to PB1 protein was analyzed using in silico molecular docking. Twenty-five compounds were tentatively identified. Total phenolic and flavonoid contents represented 49.41 ± 0.66 and 23.37 ± 0.23 µg/mg dried flower extract, respectively. The extract showed selective cytotoxicity against Caco2 cells but its main effect goes beyond mere cytotoxicity. It showed strong inhibition of P-glycoprotein, which helps to overcome multidrug resistance to classical chemotherapeutic agents. In silico molecular docking showed that dicaffeoyl quinic acid, kaempferol-O-rutinoside, rutin, and isorhamnetin-O-rutinoside exhibited the most potent inhibitory activity to PB1 involved in tumor progression. Euryops pectinatus flower heads could have promising selective cytotoxicity alone or in combination with other chemotherapeutic agents to counteract multidrug resistance.
Highlights
The development of drug resistance during cancer chemotherapy limits the survival rate of cancer patients [1]
P-gp belongs to the first member of the ATP-binding cassette (ABC) superfamily, which is encoded by the MDR1 gene [2], and is widely expressed in epithelial cells of normal tissues that are involved in drug disposition, including the liver, intestine, and kidney
Multidrug resistance (MDR) cells when applied in combination with doxorubicin
Summary
The development of drug resistance during cancer chemotherapy limits the survival rate of cancer patients [1]. Multidrug resistance (MDR) renders cancer cells immune to standard treatments. Molecules 2020, 25, 647 with various anti-cancer drugs and is a major limitation of cancer therapy [2]. To overcome MDR in cancer treatment, many strategies have been proposed, including chemotherapy with a combination of anti-tumor drugs and an inhibitor of P-glycoprotein (P-gp) and other ABC transporters. P-gp belongs to the first member of the ATP-binding cassette (ABC) superfamily, which is encoded by the MDR1 gene [2], and is widely expressed in epithelial cells of normal tissues that are involved in drug disposition, including the liver, intestine, and kidney. The intracellular concentration of some commonly used anticancer drugs is reduced by P-gp and other ABC transporter, including vincristine, etoposide, and doxorubicin [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
